The objective of the proposed research is to determine the metabolism, particularly the metabolic activation, of pesticides in primary hepatocyte cultures from laboratory animals and humans. Specifically, the metabolism of two well studied pesticides, chlordane and parathion will be investigated in hepatocytes from mice, rats, dogs, and humans. Similar studies have been done with cell-free fractions, but primary hepatocyte cultures should better reflect the in vivo metabolism of pesticides since cell architecture, cofactor levels and enzyme levels are similar to the in vivo state. Where differences in the metabolism of a pesticide are correlated with species susceptibility to its toxic action, knowledge of the metabolism of the pesticide in cultured hepatocytes from laboratory animals and humans should provide a better extrapolation of toxicity data from laboratory animals to humans.